Detoxifying antimicrobial molecular complex

ABSTRACT

The invention relates to a food additive which includes at least one clay interspersed with volatile antimicrobial agents. Such an additive can be added to the feed of certain animals, in particular poultry and ruminants, in order to act as a growth promoter and to reduce the risks of infection, as well as the risks of intoxication by mycotoxins.

CROSS-REFERENCE TO RELATED APPLICATION

This application is the U.S. national stage application of InternationalPatent Application No. PCT/MA2013/000054, filed Dec. 31, 2013.

The present invention relates to an additive for a veterinary feed, acomposition containing this additive as well as the method formanufacturing this composition and the use of this composition as anadditive with multiple actions: growth promoter action, plus protectiveaction against parasitic diseases, plus adsorbing action of mycotoxins,plus immunostimulating and intestinal and hepatobiliary protectiveaction.

Pathologies which affect animals are generally multifactorial phenomenain which several elements are involved: bacteria, viruses, fungi,parasites, immunodeficiency, metabolism, physiology, zootechnicalenvironment, dietary deficiencies, toxins and others. The breedergenerally has various products which each treat one or two factorsalone. He is therefore forced to compose cocktails from these products.This has the consequence of risk of inadequacy of treatment by excess orlack, generating diverse losses. The most used administration route forthese treatments is the oral route by addition in the feed or drinkingwater.

Cattle feed inter alia contains antibiotics used as growth promoters andantiparasitic agents like a preventive treatment for coccidiosis orhistomoniasis and other parasitic diseases. These chemotherapeuticagents are questioned in several problems of animal health and publichealth for their toxicity, the residues which they may generate in foodproducts of animal origin and their involvement in the emergence ofresistance to infectious agents (Cháfer-Pericás et al., Food Control 22(2011) 993-999).

It is for all these reasons that these agents were banned in severalregions of the world. IP/05/1687, Brussels, Dec. 22, 2005.

Cattle feed also contains non-negligible concentrations of mycotoxinsoriginating from mold which contaminate the cereals contained in thecattle feed. These mycotoxins have deleterious effects on animal healthand their residues in foods of animal origin are deleterious for thehealth of the consumer (Wayne and Bryden, Animal Feed Science andTechnology 173 (2012) 134-158).

In this context, the cattle feed manufacturers and breeders confrontedwith problems of delayed growth and parasitic diseases are forced tofind alternatives for replacing the antibiotics used as growth promotersand the antiparasitic agents which have been banned as additives in thefeed. They also have to find additives for combating the negativeeffects related to the presence of mold which produces mycotoxins andthe mycotoxins themselves (Placinta et al., A review of worldwidecontamination of cereal grains and animal feed with Fusarium mycotoxins,Animal Feed Science and Technology, Volume 78, Issue 1, Pages 21-37, 31Mar. 1999).

In order to prevent these mycotoxins from passing into the bloodstream,several means are used. The most used means is the use of adsorbentssuch as hydrated sodium calcium aluminosilicate (HSCAS), activated coal,yeast walls, phyllosilicates, cholestyramine, and lactic bacteria(Phillips, Clement and Park, 1994, Approaches to reduction of aflatoxinsin foods and feeds, in D. L. Eaton & J. D. Groopman, eds., Thetoxicology of aflatoxins—human health, veterinary and agriculturalsignificance, p. 383, San Diego, Calif., United States, Academic Press).

Clays activated by the addition of acids and by heating are among thoseadsorbents (EP 1 333 919 B 1, Use of activated layered silicates for theadsorption of mycotoxins). However, the activation processes are verycomplicated and very expensive, which has a negative repercussion on thequality and reproducibility of the capability of adsorbing mycotoxinsand makes the price of clays too expensive, especially when this iscattle feed.

Another problem related to activated clays consists of the fact thatthese clays may act as chelators of vitamins and reduce the amount ofvitamins available for the animal. This may generate problems of vitamindeficiencies.

Among the alternatives used for replacing the antibiotics andantiparasitic agents, one finds essential oils and their majoritycompounds such as thymol, carvacrol, cinnamaldehyde, eugenol and others(Alleman et al., The use of essential oils in poultry feed, INRAProductions Animales, 2013, No. 1; Bento et al., Essential oils andtheir use in animal feeds for monogastric animals, Veterinarni Medicina,58, 2013 (9): 449-458; Brenes and Roura, Animal Feed Science andTechnology, 158 (2010) 1-14).

However, these substances are volatile and therefore unstable in thefeed. This instability is at the origin of a significant loss ofessential oils during the manufacturing of the feed. This forces cattlefeed manufacturers to add large amounts of essential oils in excess sothat the feed, once it is manufactured, still contains the requiredamount of essential oils, or to use complicated and expensivestabilization methods such as microencapsulation (de Barros Fernandes etal., Gum arabic/starch/maltodextrin/inulin as wall materials on themicroencapsulation of rosemary essential oil, Carbohydrate Polymers 101(2014) 524-532).

This instability is also at the origin of the short period of validityof the sought actions in cattle feed after manufacture. This has anegative repercussion on the quality of the feed containing theessential oils as an additive and increases the price of the additive,which reduces its competitiveness with antibiotics, antiparasitic agentsand other alternatives.

The object of the present invention therefore consists of inventing astable composition containing compounds having an antibiotic(antibacterial) and antiparasitic activity, an anti-fungal activitycapable of inhibiting the growth of fungi secreting mycotoxins and atthe same time the capability of adsorbing mycotoxins. Another object ofthe invention consists of selecting, from among substances having theactivities mentioned above, those which also have an intestinal andhepatobiliary protective and immunostimulating activity.

Thus, against pathologies which are multifactorial phenomena affectinganimal health, the invention proposes a solution with multiple actions.

The composition which is the object of the present invention andintended to achieve the aforementioned goal results from complexation byinterspersing volatile molecules such as thymol, cresol, carvacrol,menthol, eugenol, and cinnamaldehyde, having an antibacterial,antiparasitic, antifungal and intestinal, hepatobiliary protective andimmunostimulating activity with clays. The clay has at the same time theaction of a stabilizer excipient of the composition, the action ofadsorbing mycotoxins and the action of intestinal protectors.

The expression “molecular complex” refers to any composition obtained bymixing essential oils or one of their volatile compounds with any edibleclay, the molecules of which are capable of interacting with theseessential oils and their volatile compounds.

The expression “essential oils” refers to any extract obtained fromaromatic plants by one of the known extraction methods allowing them tobe extracted.

The expression “volatile compounds of the essential oils” refers to anyvolatile molecule obtained by purification from essential oils or fromanother natural source or else by identical chemical synthesis, as wellas their derivatives and isomers.

The expression “edible clay” refers to any natural or synthetic mineralsubstance having a molecular structure identical or similar to that ofedible clays commonly used in the agrifood and pharmaceutical field.

The expression “interspersed clay” refers to any situation whereinterspersing molecules come into interaction with clay molecules bybeing inserted into the interfoliar spaces of clay, this interspersionbeing expressed by an increase in the interfoliar distance.

The expression “antimicrobial activity” refers to any inhibitory ordestructive action on microbial germs of a bacterial, fungal, parasiticor viral nature.

The expression “intestinal and hepatobiliary protector” refers to anyaction allowing to preserve the physical and physiological integrity ofthe intestine and to stimulate the hepatic function so as to increaseits detoxification activity.

The expression “immunostimulating” refers to any activity allowing toreinforce natural or acquired defenses of the organism.

The expression “adsorbing toxins” refers to any activity allowing thebinding of the toxins at the intestinal level in order to prevent theirabsorption into the bloodstream.

Animal husbandry is confronted with a multitude of risk factors of thezootechnical, infectious, sanitary, hygienic, immune, physiological andfeed order which promote the occurrence of pathologies which only one ofthese factors could not cause. It is for this reason that scientistsagree on the idea that the occurrence of any disease is a multifactorialphenomenon (Sjaak de Wit, Practical epidemiology of poultry disease andmultifactorial conditions, Poultry Diseases (Sixth Edition), 2008, Pages492-509).

Hence the benefit of studying the impact of each factor separately andof providing a curative or preventive remedy to each of them in order toprevent the outbreak of the disease or to attenuate the damages which itcauses. The multitude of remedies poses problems of cost, dosage of eachremedy and many other problems which complicate the work of the breeder.

In order to overcome the problem of the use of antibiotics andantiparasitic agents of chemotherapy banned by regulations and theproblem of multiple remedies, the object of the present invention istherefore a stable composition comprising a molecular complex containingnatural molecules having multiple pharmacological, antimicrobial,immunostimulating, cholagogue, and carminative activities, such asthymol, cresol, carvacrol, menthol, eugenol, cinnamaldehyde, or anycomponent containing them separately or mixed, as well as the isomers,derivatives and mixtures thereof. These volatile molecules are bound andstabilized by interspersion into the inferfoliar space of clays havingproperties for adsorption of toxins, intestinal protectors, andhydrating properties such as stevensite, bentonite, kaolinite, smectite,illite, chlorite, montmorillonite, laponite, beidellite, nontronite,saponite, sauconite, hectorite, halloysite, vermiculite, or sepiolite ortheir natural or caused interlayered mixtures.

In a particular embodiment, the composition may comprise said volatileantimicrobial agents which are antiseptic aromatic alcohols selectedfrom thymol, cresol, carvacrol, menthol, eugenol, cinnamaldehyde, or anycomponent containing them separately or mixed as well as the isomers,derivatives and mixtures thereof. These agents are interspersed inedible clays selected from stevensite, bentonite, kaolinite, smectite,illite, chlorite, montmorillonite, laponite, beidellite, nontronite,saponite, sauconite, hectorite, halloysite, vermiculite, or sepiolite ortheir either natural or caused interlayered mixtures.

Said volatile antimicrobial agent is present in said composition in aweight ratio ranging from 0.005 to 0.33 compared to said edible clay.

The method for manufacturing said composition comprises the followingsteps:

i) Said volatile antimicrobial agent is put into solution in an organicor mineral solvent in order to obtain the antimicrobial solution.

ii) Said thereby obtained antimicrobial solution is mixed with saidedible clay as a powder or pellets under stirring and temperatureconditions, giving the possibility of obtaining a homogeneous and stablecomposition formed by a molecular complex containing said edible clayinterspersed by said volatile antimicrobial agent.

In a particular embodiment, this manufacturing method may be detailed asfollows:

-   -   An amount of volatile antimicrobial agent is gradually put into        solution in an amount of vegetable or mineral oil, representing        1 to 20% of the amount of volatile antimicrobial agent, stirred        and heated to a temperature ranging from 30 to 80° C. in order        to obtain a homogeneous and limpid liquid solution, a so-called        antimicrobial solution.    -   An amount of the antimicrobial solution is gradually included by        mixing in an amount of said powdered edible clay, representing        at least three times the amount of antimicrobial solution, in        order to obtain a sievable powder.    -   The obtained sievable powder is calibrated by sieving in order        to obtain the desired grain size.

In a particular embodiment, the volatile antimicrobial agent may bethymol alone or mixed with one or several other volatile antimicrobialagents such as cresol, eugenol, carvacrol, cineol, menthol orcinnamaldehyde or any essential oil containing them separately or mixedand the edible clay may be stevensite or bentonite or their mixture orthe mixture of substances containing them.

In a preferred embodiment, the preparations as detailed above will beintended to be diluted in cattle feed for administration to an animal.This dilution may be carried out in a ratio ranging from 50 grams ofpreparation per metric ton of feed to 10 kilograms of preparation permetric ton of feed.

In a further preferred embodiment, said preparation, before dilution inthe feed, may contain the volatile antimicrobial agent at a weight ratioranging from 0.1 to 0.33 compared to the edible clay, preferentially ina weight ratio from 0.15 to 0.2 compared to clay.

One object of the present invention is the use of said composition as afeed additive for animals, added to the feed and taken via an oralroute.

In every case, the use of said compositions as feed additives isintended to exert a multitude of actions emanating from the propertiesof the substances which they contain, e.g.:

-   -   the growth-promoting activity due to the antiseptic properties        of the volatile antiseptic agents capable of reducing pathogenic        or commensal intestinal flora;    -   the antiparasitic, anticoccidian and antihistomoniasis activity,        in particular due to the antiparasitic activity of the volatile        antimicrobial agents;    -   the antifungal activity due to the antifungal activity of the        volatile antimicrobial agents, giving the possibility of        inhibiting the fungi responsible for production of mycotoxins;    -   the mycotoxin adsorption activity due to the chelating        properties of clays;    -   the cholagogue activity due to the pharmacological properties of        the volatile antimicrobial agents;    -   the immunostimulating activity due to the pharmacological        properties of the volatile antimicrobial agents; and    -   the protective intestinal activity due both to the intestinal        bandage properties of the clay and the antiseptic intestinal        properties of the volatile antimicrobial agents.

In every case, the use of said compositions as feed additives intendedto exert a multitude of favorable actions on the animal's body has theconsequence of preserving intestinal, hepatobiliary and immune integritywith positive repercussions on preserving the general health of theanimals receiving said compositions as feed additives.

The examples which follow are intended to illustrate certain aspects ofthe invention without, however, being limiting.

On the one hand, the inventor proceeded with experiments with differenttypes of volatile antimicrobial agents and different types of clays. Theresults gave the possibility of showing a displacement of thediffraction x-ray peaks of the characteristic molecules of the claystested, i.e., stevensite and bentonite, in a direction which shows anincrease in the interfoliar distance of interspersed clays by volatileantimicrobial agents as compared with clays before interspersion. Thisjustifies and explains the perfectly stable bond of the volatileantimicrobial agents on the clays when they are mixed according to themethod that is the object of the invention. On the other hand, theinventor tested the efficiency of the composition with particularlyeffective doses and ratios of the composition under in vitro and in vivoconditions.

EXAMPLE 1: X-RAY DIFFRACTION TEST

Preparations of a final weight of 1,000 grams were made with 150 gramsof thymol put into solution according to the method of the inventionwith 20 milliliters of table oil at a temperature of 60° C. Theantiseptic solution obtained thereby was mixed with 830 grams ofMoroccan ghassoul, 830 grams of Moroccan bentonite, or 830 grams of a50%/50% ghassoul/bentonite mixture (preparation a).

Control compositions were prepared:

Preparation b: The same pure clays without any additive.

Preparation c: The same clays with 20 ml of table oil alone.

Preparation d: The same clays with thymol alone as a crystallizedpowder.

Preparation e: The same clays with liquefied thymol by heating to 60° C.without any vegetable oil.

Preparations a, b and c were subjected to an x-ray diffraction testaccording to the usual standards for treating clays in this analyticalmethod.

The results obtained show a displacement of the specific peaks ofbentonite and stevensite in the spectrum, in a surprising way in thecase of the preparations according to the method of the invention(preparation a) as compared with the controls of pure clays (preparationb) and clays having been mixed with table oil alone (preparation c)(results in Table 1). At the same time, the results show that forpreparation d containing thymol as a crystallized powder mixed withclay, the obtained powder is heterogeneous and the obtained x-raydiffraction spectrum was not able to be utilized. For preparation e, inwhich thymol was liquified by heating and mixed with clay without anyvegetable oil, it is seen that thymol recrystallizes and forms hardlumps. The mixture obtained thereby is heterogeneous and cannot meet thecriteria for which the invention was elaborated.

This shows on the one hand that the manufacturing method used in theinvention actually gives the possibility of ending up with interspersionof thymol in the interfoliar spaces of the clays, which leads to astable and homogeneous dispersion of thymol in clay and an increase inthe distance of the interfoliar spaces of the clays, therefore improvinghydrophobicity and the capability of the clays of adsorbing the toxins.

These results show on the other hand that the mixtures with thymol andclay by obvious methods using crystallized thymol or liquified thymol byheating do not end up with the result expected by the invention.

TABLE 1 Interfoliar distance of the clays according to the preparationmodes a, b and c. Bentonite Stevensite With With With table oil and Withtable oil and Crude table oil essential oil Crude table oil essentialoil Clays (prep. b) (prep.c) (prep. a) (prep. b) (prep. c) (prep. a)Distance 15.23 15.23 15.69 15.75 16.15 16.51 between sheets (inangstroms)

EXAMPLE 2: IN VIVO TEST

Batches of 25 young broilers and 12 turkey poults were fed with a feedcontaining the preparation of the invention in an amount of 100 grams,500 grams, 1 kilogram or 2 kilograms per metric ton of feed. Controlbatches of the same size were fed with a feed not containing anyantibiotic or antiparasitic agents. Other control batches of the samesize were fed with a feed containing Flavomycin in an amount of 200grams per metric ton of feed and Salinomycin in an amount of 70 gramsper metric ton of feed for the broilers and 100 grams per metric ton ofmonensin for the turkey poults. During five weeks of treatment, fecessamples of each subject in each batch were analyzed by microscopy and bysuitable microbiological analysis for evaluating the numbers ofbacteria, yeast, fungi and oocytes of protozoa, in particular of thespecies Eimeria. sp., involved in coccidiosis in chickens and turkeys.At the end of the five weeks of the experiment, the subjects weresacrificed and autopsies were carried out by professional veterinarians,specialists in avian pathology. The goal of the autopsies was toevaluate the lesional scores of the intestine and the integritycondition of the liver, kidneys, lungs, spleen and intestine.

The results obtained show highly significant reductions in the numbersof bacteria, yeasts, fungi and oocytes in the batches having receivedthe preparation of the invention in their feed at doses of 1 kilogramper metric ton and 2 kilograms per metric ton as compared with controlbatches having received a neutral feed. The batches having received thepreparation of the invention in their feed at doses of 100 grams and 500grams per metric ton of feed did not have any significant difference ascompared with the control. The batches having received the antibioticand the antiparasitic agent in their feed have a visible butnon-significant reduction as compared with the controls. However, thenumbers of bacteria, yeasts, fungi and oocytes in batches havingreceived the preparation of the invention at the doses of 1 kilogram and2 kilograms per metric ton of feed is significantly less than the numberof bacteria, yeasts, fungi and oocytes recorded in the batches havingreceived the antibiotic and the antiparasitic agent in the feed. Theseresults show that the preparation according to the invention used as anadditive in chicken and turkey feed has multiple activities likepromoting growth (reduction in the intestinal flora), as anantiparasitic (anticoccidian) agent and as an antifungal agentsignificantly superior to the antibiotics and antiparasitic agents usedin this test. The results of the autopsies also show that the intestinallesion, kidney, lung, spleen and liver congestion scores aresignificantly lower in the batches having received the feed containingthe preparation of the invention as compared with the batches havingreceived the neutral feed or the feed containing the antibiotic and theantiparasitic agent. These results again show that the preparation ofthe invention used as an additive in chicken and turkey feed hasactivities protecting intestinal integrity, hepatobiliary protectiveactivities, and activities purifying the lungs and kidneys andprotecting the spleen. These results confirm that the preparation of theinvention represents a solution with multiple activities for combatingpathologies of chickens and turkeys which are multifactorial diseases.

Batches of 25 chicks of one day of age were fed for 5 weeks on averagewith respectively:

-   -   batch 1: a white “broiler” feed which contains neither        antibiotics nor antiparasitic agents;    -   batch 2: a feed containing a growth factor antibiotic,        “Flavomycin,” in an amount of 200 milligrams per kilogram of        feed and an antiparasitic agent, “Salynomycin,” in an amount of        70 milligrams per kilogram;    -   batch 3: a feed containing the preparation of the invention in        the feed at a proportion of 100 grams per metric ton of feed;    -   batch 4: a feed containing the preparation of the invention in        the feed at a proportion of 500 grams per metric ton of feed;    -   batch 5: a feed containing the preparation of the invention in        the feed at a proportion of 1 kg per metric ton of feed; and    -   batch 6: a feed containing the preparation of the invention in        the feed at a proportion of 2 kg per metric ton of feed.

TABLE 2 Zootechnical and microbiological results of the broiler in vivotest Con- Mor- sump- Body Bacterial load Fungal load tality tion weight(CFU/g of (CFU/g of rate index (g) faeces) faeces Batch 1 0% 2.3 105 ±8.6  1 · 10¹⁰ ± 0.3 8.6 · 10⁹ ± 3.7 Batch 2 0% 2.2 110 ± 6.4 4.9 · 10⁹ ±2.1 1.6 · 10⁹ ± 0.3 Batch 3 0% 2.2 113 ± 3.4 4.5 · 10⁹ ± 3.2 5.7 · 10⁸ ±1.2 Batch 4 0% 2.1 121 ± 4.5 3.2 · 10⁸ ± 4.1 1.3 · 10⁸ ± 0.3 Batch 5 0%1.9 138 ± 6.6 7.3 · 10⁷ ± 5.2 8.6 · 10⁷ ± 1.5 Batch 6 0% 1.8 157 ± 2.2  2 · 10⁷ ± 1.70  5 · 10⁷ ± 1.1

The in vivo test for turkeys gave similar results to those obtained inthe broiler chicken in vivo test.

EXAMPLE 3: FIELD TESTS

Field tests were carried out on a farm raising chicken broilers and afarm raising turkey broilers. In these tests, two batches of 13,500chicks each received the preparation of the invention at the dose of twokilograms per metric ton of feed during the whole duration of the tape(40 days for chickens and 13 weeks for turkeys). Two other batches of13,500 chicks each received the preparation of the invention at the doseof 1 kilogram per metric ton of feed and two other batches of 13,500chicks each received a feed containing the antibiotic Flavomycin at 200grams per metric ton of feed and the antiparasitic agent Salynomycin at70 grams per metric ton of feed for chickens and monensin for turkeys.At the end of the strip, the zootechnical performances and the lesionscores were measured for each batch.

The results show:

Mortality: The percentage of dead chickens and turkeys during theraising cycle was 2.9% for chickens and 2.5% for turkeys for the batcheshaving received 1 kilogram or 2 kilograms of preparation of theinvention per metric ton of feed. For the batches having received theantibiotic and the antiparasitic agent in the feed, the mortality was5.2% for turkeys and 5.9% for chickens.

Average weight: The average weight of both batches having received 1kilogram or 2 kilograms per metric ton of feed of the preparation of theinvention is 2.3 kg per subject in chickens and 12.8 kg in turkeys; thatof the two batches having received the antibiotic and the antiparasiticagent was 2.135 kg in chickens and 11.9 kg in turkeys.

Consumption index: The consumption index for the batches having receivedtwo kilograms of the preparation of the invention per metric ton of feedwas 1.68, that of the batches having received one kilogram of thepreparation per metric ton of feed was 1.82, and that of the two batcheshaving received the antibiotic and the antiparasitic agent was on theorder of 1.98.

The titers of the antibodies related to the vaccines used: Theinhibition titer of hemagglutination as compared with the antibodies ofthe viruses of Newcastle's disease the batches having received thepreparation in an amount of two kilograms and one kilogram per metricton of feed was 64, 64, 64, 32 respectively and, for the two batcheshaving received the antibiotic and the anti-coccidian agent, were 16 and16.

The lesional score of the intestine: The lesional scores of theintestine were lowest (1.22) for the batches having received thepreparation of the invention in an amount of 2 kg and 1 kg while thescores for the batches having received the antibiotic and theanti-coccidian agent were on the order of 2.74 and 3.13.

The score of the integrity of the organs: The aspect of the organs(liver, spleen, lungs, muscles and bones) were clearly more healthy (notshowing any sign of congestion) for the batches having received thepreparation of the invention in an amount of 2 kg and 1 kg per metricton of feed, while congestion signs visible to the naked eye wereascertained in the majority of the autopsies in both batches havingreceived the antibiotic and the antiparasitic agent.

These results surprisingly show that the preparation of the inventionexerts the multiple activities for which it was designed even underintensive raising conditions in the field.

EXAMPLE 4: INHIBITION AND ADSORPTION OF MYCOTOXINS IN FEED AND CORN

Samples of corn and composed feed were treated with variable amounts ofthe preparation of the invention in the proportions of 2 kg, 4 kg and 6kg per metric ton of feed. These samples were hermetically packaged andincubated at a temperature of 27.5° C. 50 gram aliquots were taken afterfour weeks for dosage of the mycotoxins; the results show that the cornsamples having been treated by the preparation of the invention hadsignificantly lower levels of DON (deoxynivalenol), ZON (Zearalenone)and ochratoxin than the control sample. This inhibition and adsorptioneffect on mycotoxins is increased according to the dose used of thepreparation of the invention. A similar result was obtained for thecomposed feed sample treated by the preparation of the invention withrespect to the untreated sample for mycotoxins, ochratoxin (ZON) andaflatoxin.

These results show that the preparation of the invention also has thecapability of protecting feed and corn from mycotoxins which represent asignificant risk factor promoting the outbreak of diseases and causing,in acute cases, mortal intoxication of animals.

TABLE 3 Percentage of reduction of the mycotoxins in corn treated withthe preparation of the invention as compared with the untreated control.Preparation 0.2 g/100 0.4 g/100 0.6 g/100 Mycotoxins g of corn g of corng of corn Zearalenone 56% 59% 61% DON 63% 73% 75% ochratoxin 13% 22% 27%

TABLE 4 Reduction percentage of the mycotoxins in the treated composedfeed with respect to the untreated control. Preparation 0.2 g/100 0.4g/100 0.6 g/100 Mycotoxins g of feed g of feed g of feed Zearalenone  35% 63% 94% Aflatoxin 74.35% 86% 89%

The invention claimed is:
 1. A composition combining both antimicrobialand toxin-adsorption activities, characterized in that it is formed by amolecular complex comprising an edible clay interspersed by a volatileantimicrobial agent, characterized in that said edible clay is a mixtureof Ghassoul from Morocco and bentonite from Morocco.
 2. The compositionaccording to claim 1, characterized in that said volatile antimicrobialagent is an antiseptic aromatic alcohol selected from thymol, cresol,carvacrol, eugenol, menthol, cinnamaldehyde or mixtures or isomersthereof.
 3. The composition according to claim 1, characterized in thatsaid volatile antimicrobial agent is formed by a mixture of two or morenatural or synthetic antimicrobial agents.
 4. The composition accordingto claim 1, characterized in that said mixture of Ghassoul and bentonitefrom Morocco contains at least 5% by weight Ghassoul from Morocco. 5.The composition according to claim 1, characterized in that saidvolatile antimicrobial agent is present in a mass ratio from 0.005 to0.33 based on said edible clay.
 6. A method for manufacturing acomposition comprising an edible clay and a volatile antimicrobial agentcomprising: i) adding said volatile antimicrobial agent into solutionwith an organic or mineral solvent in order to obtain an antimicrobialsolution; and ii) mixing said antimicrobial solution with said edibleclay as a powder or pellets under stirring and temperature conditions toobtain a homogenous and stable composition formed by a molecular complexcontaining said edible clay interspersed by said volatile antimicrobialagent, characterized in that said edible clay is a mixture of Ghassoulfrom Morocco and bentonite from Morocco.
 7. The manufacturing methodaccording to claim 6, characterized in that said volatile antimicrobialagent is selected from thymol, cresol, carvacrol, menthol, eugenol,cinnamaldehyde, or mixtures or isomers thereof, said organic or mineralsolvent is a vegetable oil.
 8. The manufacturing method according toclaim 6 wherein: crystallized thymol is gradually put into solution in avolume of vegetable oil heated to a temperature allowing it to melt soas to obtain a homogeneous and limpid liquid composition (anantimicrobial solution); mixing said antimicrobial solution with anamount of said edible clay as a powder capable of absorbing it in orderto obtain a molecular complex as a homogenous and stable powder; andsubjecting said powder to a calibration or sieving operation to obtainthe desired grain size.
 9. The manufacturing method according to claim6, characterized in that the volatile antimicrobial agent is a mixtureof thymol and cresol.
 10. The manufacturing method according to claim 6,characterized in that the volatile antimicrobial agent is a mixture ofthymol, cresol and menthol.
 11. A method of reducing or suppressing thedevelopment of pathogenic or toxinogenic germs in an animal comprisingadministering a composition according to claim 1 to an animal or itssurroundings.
 12. The method according to claim 11, wherein saidcomposition is administered to said animal in a feed containing saidcomposition.
 13. The method according to claim 11, wherein saidcomposition is added to feed, drinking water, litter, walls of theanimal enclosure, barn area, rearing equipment or the vehiclestransporting the animal.
 14. The method according to claim 11, whereinsaid animal is a mammal, fish, bee or poultry.
 15. The method accordingto claim 14, wherein said mammal is a bovine animal, ovine animal,rabbit, pig, caprine animal or equine animal.
 16. The method accordingto claim 14, wherein said poultry are selected from chicken broilers,laying hens, breeding roosters and hens, guinea fowl, turkeys, quail,ducks, geese and pigeons.
 17. The method according to claim 11, saidmethod reducing or suppressing development of bacteria, fungi,parasites, bacteriotoxins and mycotoxins in the animal.